Abstract
Dimethylations of histone H3 lysine 9 and lysine 27 are important epigenetic marks associated with transcription repression. Here, we identified KIAA1718 (KDM7A) as a novel histone demethylase specific for these two repressing marks. Using mouse embryonic stem cells, we demonstrated that KIAA1718 expression increased at the early phase of neural differentiation. Knockdown of the gene blocked neural differentiation and the effect was rescued by the wild-type human gene, and not by a catalytically inactive mutant. In addition, overexpression of KIAA1718 accelerated neural differentiation. We provide the evidence that the pro-neural differentiation effect of KDM7A is mediated through direct transcriptional activation of FGF4, a signal molecule implicated in neural differentiation. Thus, our study identified a dual-specificity histone demethylase that regulates neural differentiation through FGF4.
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10 July 2025
A Correction to this paper has been published: https://doi.org/10.1038/s41422-025-01143-2
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Acknowledgements
We thank Anning Lin (The University of Chicago) for the critical reading of the paper, members in the Chen lab for technical help, the cell biology and molecular biology core facilities for confocal study and Q-PCR, and Shanghai Biochip Co Ltd. for microarray analysis. The H3K27me2 antibody was kindly provided by Li Tang (Fudan University) and Thomas Jenuwein (Research Institute of Molecular Pathology, The Vienna Biocenter). This work was supported by the National Basic Research Program of China (2007CB957900, 2006CB943902, 2007CB947101, 2008KR0695, 2009CB941100, 2005CB522704), the Chinese Academy of Sciences (KSCX2-YW-R-04), the National Natural Science Foundation of China (90919026, 30870538,30623003, 30721065, 30830034, 90919046), the Shanghai Pujiang Program (0757S11361), the Shanghai Key Project of Basic Science Research (06DJ14001, 06DZ22032, 08DJ1400501), and the Council of Shanghai Municipal Government for Science and Technology (088014199).
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The original online version of this article was revised: Figure 4 was corrected.
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Supplementary information, Figure S1 (download PDF )
Gene Ontology (GO) hierarchy for enriched biological process categories. (PDF 206 kb)
Supplementary information, Figure S2 (download PDF )
Knockdown of KIAA1718 blocked neural differentiation. (PDF 144 kb)
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Huang, C., Xiang, Y., Wang, Y. et al. Dual-specificity histone demethylase KIAA1718 (KDM7A) regulates neural differentiation through FGF4. Cell Res 20, 154–165 (2010). https://doi.org/10.1038/cr.2010.5
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DOI: https://doi.org/10.1038/cr.2010.5
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